EP2652488B1

EP2652488B1 - Single-use bioreactor comprising a unitary plastic conductivity sensor

Info

Publication number: EP2652488B1
Application number: EP11815603.3A
Authority: EP
Inventors: Chang-Dong Feng; Barry W. Benton
Original assignee: Rosemount Analytical Inc
Current assignee: Rosemount Inc
Priority date: 2010-12-15
Filing date: 2011-12-15
Publication date: 2023-04-05
Anticipated expiration: 2031-12-15
Also published as: US9029130B2; US20120178151A1; AU2011343773A1; WO2012082970A1; EP2652488A1; CN202676808U; AU2011343773B2; CA2821332A1; CN103163384B; CN103163384A; CA2821332C

Description

BACKGROUND

Liquid conductivity measurement systems are used for measuring the conductivity of water and aqueous or non-aqueous solutions in environmental, medical, industrial, and other applications where an indication of the ionic content of the liquid is required.
Liquid conductivity is measured in a variety of contexts to provide a parameter that can be related to bulk ionic concentration. In situations where a single type of ion is present, the conductivity can actually be related to the specific ionic concentration. Even in situations where a number of different ionic compounds are present, the measurement of bulk liquid conductivity can still provide very useful information. Accordingly, there has been widespread adoption and utilization of conductivity measurement by the industry for a variety of different purposes.
Typically, contact-based conductivity measurement systems include a conductivity cell and an associated conductivity meter. FIG. 1 illustrates such a system. A conductivity meter generates an AC voltage that is applied to the electrodes of the conductivity cell. The meter then senses the resultant current flow between the electrodes of the cell. This current is generally a function of the conductivity of the liquid to which the cell is exposed.
The amount of current that flows between the electrodes depends not only the solution conductivity, but also on the length, surface area, and geometry of the sensor electrodes. The probe constant (also called sensor constant or cell constant) is a measure of the current response of a sensor to a conductive solution, due to the sensor's dimensions and geometry.
Contact-type conductivity sensors are generally made from at least two pairs of metallic electrodes spaced apart in an insulating sensor body. The distance between and surface area of the electrodes are defined. During operation, the electrodes are in direct contact with the sample solution. The conductivity of the sample solution can be measured by using either a two-electrode or a four-electrode method.
U.S. Patent Publication No. 2006/011474 discloses a device for detecting an analyte in a liquid. The device comprises a multitude of electrodes that are insulated from one another by being arranged in an electrically non-conductive material that is impermeable to the liquid. The electrodes have an analyte-specific coating or analyte-specific molecules. The reference further teaches methods of encapsulation of elongated solid electrode materials with an insulating material surrounding the electrode materials.
US 2010/326842 discloses electrode structures and integrated electrode structures having one or more conductive materials coextruded with one or more dielectric materials. The disclosed electrode structures can be configured for use as analyte sensors. Also provided, are methods of making and using the electrode structures and integrated electrode structures described herein. DE 10 2008 054659 discloses that in a conductive conductivity sensor with a probe which can be immersed into a measuring medium and which comprises at least two electrodes made of a first electrically conductive material and at least one probe body are embedded in the probe body the electrodes being at least partially insulated from each other, the electrodes and the probe body are designed as a composite workpiece. In particular, there is a strong bond between the first material and the second material in at least one subregion of a material transition between the first and the second material, in particular by intermolecular interactions or chemical bonds.
Conventional manufacturing methods rely on metal in the form of thin/thick film, or a rod as the electrode, and plastic, or ceramic/glass, as the sensor body materials. Issues have risen with conventional manufacturing methods including cost and leakage between the seal and sensor body materials.
Providing a contact-type conductivity sensor that is not only lower cost than previous contacting-type conductivity sensors, but more resistant to leaks that would represent a significant advance for contact-type conductivity sensors.

SUMMARY

A single-use bioreactor comprising the features of claim 1 is disclosed. A method of forming a single-use bioreactor comprising the features of claim 8 is disclosed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a contact-type conductivity measurement system
FIGS. 2 and 3 are perspective and top plan views of a monolithic plastic conductivity sensor in accordance with an embodiment of the present invention.
FIG. 4 is a diagrammatic view of a manufacturing process for the conductivity sensor shown in FIGS. 2 and 3.
FIG. 5 is a diagrammatic view of a solid plastic conductivity sensor being used to measure the conductivity of a solution within a single-use bioreactor in accordance with an embodiment of the present invention.
FIG. 6 is cross-sectional diagrammatic view of a plastic conductivity sensor mounted to a portion of a plastic wall of a single-use bioreactor in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

FIGS. 2 and 3 are perspective and top plan views of a unitary plastic conductivity sensor 10 in accordance with an embodiment of the present invention. As used herein "plastic" is intended to mean a synthetic organic polymer that can be molded into shape while soft and then set into a rigid or slightly elastic form. Sensor 10 includes at least two and preferably four conductive electrodes 12, 14, 16, 18 disposed within insulative sensor body 20. Sensor body is illustrated having a pair of opposing faces 21, 23 and a sidewall 25 extending therebetween. Each of conductive electrodes 12, 14, 16, 18 extends from first face 21 through sensor body 20 to second face 23. In use, one of faces 21, 23 will be in direct contact with a sample solution to determine the conductivity of the sample solution. As illustrated in FIG. 3, when four electrodes are used, they are preferably collinear with one another.
The entire conductivity sensor 10 is considered unitary in that the entire sensor is constructed of plastic with no seals or material interfaces therein. Instead, the whole sensor 10 is a single plastic piece with portions thereof ( electrodes 12, 14, 16, 18) being electrically conductive. Each of electrodes 12, 14, 16, 18, and sensor body 20 is formed of a thermoplastic compound where additives, or other suitable materials are provided in the regions of electrodes 12, 14, 16, 18 to provide conductivity.
Conductive plastic compounds, such those used for electrodes 12, 14, 16, 18 are known and readily available. Some exemplary compounds are sold by RTP Company of Winona, Minnesota. The electrically conductive thermoplastic compounds available from RTP Company generally include a resin that has been modified with conductive additives, including carbon-based (powder and fibers), metal-based (solids and coatings), and all-polymerics. Compounds have been developed based in polyethylene, polypropylene, and polystyrene. Generally, such materials are used for electrostatic discharge (ESD) control with tuning capability, and mechanical properties similar to the matrix resin, and processing ease. Another all-polymeric available from RTP is sold under the trade designation Permastat PS^®. Permastat products are non-sloughing, colorable, and available in a wide array of polymers.
Many different plastic organic polymers can be compounded with conductive fillers to render them conductive. Such polymeric compounds include acetal (POM), acrylic (PMMA), fluoroplastics (PTFE, PVDF, PFA), polycarbonates (PC), polyetheretherketone (PEEK), polyolefins (polypropylene, polyethylene, polymethylpentene), polysulfone (PSU), polyethersulphone (PEC), polyurethane elastomer (TPU), and styrenics (polystyrene, ABS). The polymeric compound used for both sensor body 20 and the electrode regions is a thermoplastic. However, any suitable polymer can be used. Thermoplastics provide an important advantage, however, in that the sensor body and electrodes can be provided separately, assembled together, and heated to the thermoplastic melting point at which time all material interfaces fuse together to form a unitary whole. Thus, sensor body 20 is preferably a disc or rod that is drilled or bored to generate apertures that can receive rods that will form electrodes 12, 14, 16, 18. With rods placed within the suitable bores, the entire assembly is simply heated to the thermoplastic melting point of the sensor body and electrodes to form a unitary plastic whole. The entire assembly can then be sliced, to provide individual unitary plastic conductivity sensors 10.
FIG. 4 is a diagrammatic view of a manufacturing process for conductivity sensor 10 (shown in FIGS. 2 and 3). A rod 22 of electrically insulative plastic material is provided having a number of bores 24, 26, 28, and 30. Generation of bores 24, 26, 28, and 30 in rod 22 can be performed in any suitable manner including drilling. However, bores 24, 26, 28, and 30 can also be pre-formed in body 22 in a casting or extrusion-type process.
Conductive plastic 32, 34, 36, 38, is injected or otherwise conveyed into respective bores 24, 26, 28, 30. By injecting plastic 32, 34, 36, and 38 into respective bores, while the plastic is at a temperature above its glass transition temperature, the plastic will flow through each respective bore to fill the contours therein. Once cooled, a unitary plastic whole is formed. According to the invention, body 22 and plastic portions 32, 34, 36, 38 are formed of the same plastic compound such as acrylic, ABS, carbonate, or others. The only difference between the materials of body 22 and rods 32, 34, 36, 38 is the presence of a conductive additive provided during the formation of rods 32, 34, 36, 38 to render such rods electrically conductive.
In any event, after the plastic 32, 34, 36, 38 has been injected into respective bores and cooled, an entirely-plastic unitary article is manufactured. Individual conductivity sensors can be formed by cutting the article, for example, along cut lines 40, 42, 44, et cetera.
Although the manufacturing process set forth above with respect to FIG. 4 is illustrated with respect to inserting a number of electrically-conductive rods into an insulative plastic body and heating the body to a glass transition temperature of at least the rods or the plastic body, embodiments of the present invention can be practiced using other manufacturing methods as well. For example, embodiments can be practiced wherein the entire assembly is simply provided as a single complex extrusion. In such extrusion, the conductive plastic is fed in the regions which will thereafter become electrodes, to generate the fused assembly as a result of the extrusion process. Then, individual plastic conductivity sensors can be individually cut from the extruded whole.
Although the embodiment described with respect to FIG. 4 injected plastic into the bores of insulative body 22, embodiments of the present invention can also be practiced where insulative body 22 is injected around a plurality of conductive plastic rods while such rods are held or maintained in a mold or other suitable structure.
FIG. 5 is a diagrammatic view of a solid plastic conductivity sensor being used to measure the conductivity of a solution within a single-use bioreactor or container in accordance with an embodiment of the present invention. As used herein, single-use bioreactor or container 50 is intended to be any plastic container that is of such low cost as to be essentially disposable for processes such as bioreaction. Conductivity sensor 10 is mounted within single-use bioreactor 50 and the electrodes of sensor 10 are in contact with a specimen 52 disposed within single-use bioreactor 50. Sensor 10 is coupled via a two or four-wire connection to conductivity analyzer 54 which provides suitable energization signals to sensor 10. Analyzer 54 measures conductivity of specimen 52 using sensor 10 and provides a read-out or other suitable indication of the conductivity of the specimen 52.
One particular synergy provided by embodiments of the present invention is due to the extremely low cost required to manufacture sensor 10. The cost can be driven down to such an extent that sensor 10 can be considered disposable. Thus, the entire single-use bioreactor and sensor 10 can be disposed of after the bioreaction is complete. In this sense, sensor 10 may be considered a single-use plastic conductivity sensor.
FIG. 6 is cross-sectional diagrammatic view of a plastic conductivity sensor mounted to a portion of a plastic wall of a single-use bioreactor in accordance with an embodiment of the present invention. Wall 58 is constructed of a plastic that is bonded, either using thermal or adhesive-based bonding to single-use plastic conductivity sensor 10 at reference numeral 56. Wall 58 defines a sealable bioreaction chamber therein. Aperture 59 is created in wall 58 to allow conductors 60, 62, 64, and 66 to pass therethrough. However, bond or weld 56 creates a liquid-tight seal between sensor 10 and wall 58. While FIG. 6 shows single-use conductivity sensor 10 bonded to a wall of a single-use bioreactor, any other plastic container that requires conductivity measurement can be employed in accordance with embodiments of the present invention.
In the embodiment shown in FIG. 6, conductivity analyzer 54 is coupled to electrodes 12, 14, 16, 18 via respective wires, or conductors, 60, 62, 64, 66. Each of conductors 60, 62, 64, 66 makes electrical contact with a respective electrode 12, 14, 16, 18 through connector 61. The embodiment illustrated with respect to FIG. 6 is a four-wire embodiment in that conductivity analyzer 54 creates an electrical current or voltage between electrodes 12 and 18 and then uses electrodes 14 and 16 to measure the electrical response of the specimen or solution therein. It is also known to use a single pair of electrodes for conductivity measurements.

Claims

A single-use bioreactor (50), comprising:
a contacting-type conductivity sensor (10) comprising:
an electrically insulative thermoplastic body (20);

a plurality of conductive electrodes (12, 14, 16, 18) disposed in the thermoplastic body (20),

wherein each electrode (12, 14, 16, 18) being constructed of thermoplastic compound and co-extruded with the thermoplastic body (20);

wherein the insulative thermoplastic body (20) and a thermoplastic portion of the plurality of electrically conductive thermoplastic electrodes (12, 14, 16, 18) being formed of the same thermoplastic compound without seals or material interfaces therein,

a bioreaction chamber configured to hold a specimen;
wherein the contacting-type conductivity sensor (10) is mounted on a plastic wall within the bioreaction chamber by a bond (56) such that the electrodes (12, 14, 16, 18) of the contacting-type conductivity sensor (10) are configured to contact the specimen (52), and wherein the bond (56) liquid-tightly seals an aperture (59) within the wall (58) of the bioreaction chamber, and

wherein the aperture (59) allows conductors (60, 62, 64, and 66) that are coupled to electrodes (12, 13, 16, 18) to pass therethrough.
The single-use bioreactor (50) of claim 1, wherein said thermoplastic compound is selected from the group consisting of acetals, acrylics, fluoroplastics, polycarbonates, polyetheretherketones, polyolefins, polysulfones, polyethersulphones, polyurethane elastomers, and styrenics.
The single-use bioreactor (50) of claim 1, wherein the electrically insulative thermoplastic body (20) and the plurality of conductive electrodes (12, 14, 16, 18) are formed of a thermoset plastic.
The single-use bioreactor (50) of claim 1, wherein the plurality of conductive electrodes (12, 14, 16, 18) includes four electrodes.
The single-use bioreactor (50) of claim 4, wherein the conductive electrodes (12, 14, 16, 18) are collinear.
The single-use bioreactor (50) of claim 1, wherein the insulative thermoplastic body (20) is formed in the shape of a disc having a pair of opposing faces, and wherein each conductive electrode (12, 14, 16, 18) extends from the first face through the thermoplastic body (20) to the other face.
The single-use bioreactor (50) of claim 6, wherein one of the faces is configured to be exposed to a sample solution to measure conductivity of the sample solution.
A method of forming a unitary plastic conductivity sensor in a single-use bioreactor (50), the method comprising:
providing an electrically insulative thermoplastic body (20);

generating a plurality of apertures in the insulative thermoplastic body (20);

injecting an electrically conductive plastic into each of the plurality of apertures to form electrodes (12, 14, 16, 18), such that the molten conductive plastic material, upon solidification, comprises a plurality of conductive plastic rods formed of the same material as the thermoplastic body (20);

forming the insulative thermoplastic body and a thermoplastic portion of the plurality of electrically conductive thermoplastic electrodes from the same plastic compound without seals or material interfaces therein to form the unitary plastic conductivity sensor (10);

attaching the electrically insulating thermoplastic body (20) to a plastic wall (58) inside a bioreaction chamber by a bond (56) such that the electrodes of the unitary plastic conductivity sensor (10) are in contact with the specimen inside the single-use bioreactor (50), wherein the bond (56) seals an aperture within the wall of the bioreaction chamber, and

wherein the aperture (59) allows conductors (60, 62, 64, and 66) that are coupled to electrodes (12, 14, 16, 18) to pass therethrough.
The method of claim 8, further comprising slicing the unitary plastic conductivity sensor (10) into a plurality of discrete plastic conductivity sensors (10).
A single-use bioreactor (50) manufactured by the process of claim 8.